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Endoscopic diagnosis of segmental colonic tuberculosis
0016-5107/92/3805-0571$03.00 GASTROINTESTINAL ENDOSCOPY Copyright © 1992 by the American Society for Gastrointestinal Endoscopy
Endoscopic diagnosis of segmental colonic tuberculosis Dinesh K. Bhargava, MD, PhD, A. K. S. Kushwaha, PhD S. Dasarathy, MD, OM, Shriniwas, MD Prem Chopra, MD New Delhi, India
We report colonoscopic findings in 29 proven cases of segmental colonic tuberculosis. The colonoscopic appearances of tuberculosis included: mucosal nodules and ulcers, stricture with nodules and ulcerations, and mucosal nodules with or without pseudopolypoid folds. In 12 (41%) of 29 patients colonoscopy biopsies enabled a histologic diagnosis to be made on the basis of typical granulomas. Culture of biopsy tissue on Lowenstein Jensen media isolated Mycobacterium tuberculosis in six (40%) of 15 patients. Combined histologic and bacteriologic evaluation established the diagnosis in 60% of patients. We conclude that even though target biopsy is an effective method of diagnosis, antituberculous chemotherapy may be started on the basis of the endoscopic appearance if there is a high clinical suspicion of tuberculosis. (Gastrointest Endosc 1992;38:571-574)
Tuberculosis of the colon and rectum even though uncommon is not a rarity in India.! Its clinical manifestations are non-specific. 2,3 Segmental radiologic findings are often difficult to differentiate from other diseases. 3 ,4 Surgical biopsies have been required to establish the diagnosis. In the recent past, numerous reports have shown the value of colonoscopic biopsy for confirmation of intestinal tuberculosis. 5- 9 However, the value of colonoscopy has not been emphasized in segmental colonic tuberculosis, probably because this condition is less prevalent in developed countries. 1O-!4 The present study describes the endoscopic lesions and evaluates the value of directed biopsies in patients with proven colonic and rectal tuberculosis. MATERIALS AND METHODS
Between 1984 and 1991, 29 patients with colonic and rectal tuberculosis underwent colonoscopy. In each patient, the following data were recorded: history, clinical examination, hematologic investigation, tuberculin test, chest x-ray, barium meal or barium enema, colonoscopic findings, and Received July 16, 1991. For revision September 3, 1991. Accepted April 2, 1992. From the Departments of Gastroenterology, Microbiology, and Pathology, All India Institute of Medical Sciences, New Delhi, India. Reprint requests: D.K. Bhargava, MD, Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi 110029, India. VOLUME 38, NO.5, 1992
histologic and bacteriologic data on biopsy material. The colonoscopic diagnosis was either confirmed by histologic evidence of caseating or non-caseating granuloma or a positive culture for mycobacteria. Other criteria included the presence of an associated focus of tuberculosis elsewhere or an absence of other diseases on biopsies from the endoscopic lesions with a response to anti-tuberculous chemotherapy. Colonoscopy was carried out with Olympus model CF type LB2 or CFL 10. Eight to 10 biopsies were obtained in each patient. Histologic examination was conducted: sections of 4- to 5-/Lm thickness were sliced from paraffin blocks and stained with hematoxylin and eosin. Bacteriologic examination was performed: suitable (three to four biopsy pieces) tissue was collected aseptically in physiologic saline for isolation of organisms. The tissue obtained was cut up with scissors and ground by using a tissue grinder. Subsequently, it was subjected to concentration by the modified Hanks' method. I5 The tissue homogenate was utilized for smear examination and culture on Lowenstein Jensen media. The various biochemical tests performed for identification of the organisms have been described by Vestal. 16 RESULTS
There were 18 men and 11 women with a mean age of 34.2 years. The common symptoms were fever (86%), weight loss (86%), diarrhea (50%), constipation (41%), obstructive symptoms (21%), and rectal bleeding (70%). Hematological investigations revealed an elevated erythrocyte sedimentation rate in 90% patients (20 to 55 mm/hour). Tuberculin skin test using 571
one tuberculin unit of purified protein derivative (BCG Laboratories, Guindi Madras) was positive (> 10 mm in diameter) in 25 (86%) of 29 patients. Chest xray was abnormal in 10 (35%) of 29 patients. Four patients had pulmonary infiltration, four had thickened pleura, and two had calcified hilar lymph nodes. All of them had a barium enema which showed areas of narrowing or constricting lesions. Five of these patients had additional findings suggestive of ileocecal involvement (shortening and narrowing of the cecum, distortion of the ileocecal valve with stenosis in the pre-valvular segment of the ileum) on barium enema. Tuberculosis involved various anatomical segments of the colon as shown in Figure 1. Two or more segments were involved in eight (28%) patients. Four patients with primarily sigmoid colon tuberculosis had involvement of the ileocecal region in two and in one each, the ascending colon and splenic flexure were affected. Two patients with tuberculosis primarily involving the descending colon had additional lesions in the transverse colon and ileocecal region. Tuberculosis primarily of the splenic flexure in one patient simultaneously involved the ileocecal region. In one patient segmental tubercular lesions were present in the descending colon, transverse colon, and ileocecal region. The clinical findings in the 29 patients with colonic tuberculosis are as shown in Table 1. Colonoscopic findings
Eleven patients had mucosal nodules and ulcers in a colonic segment of 4 to 8 em. The nodules measured 2 to 6 mm and had a pink surface (Fig. 2). They were
scattered and at places densely packed. Friability of mucosa over the nodules was unremarkable. Multiple small ulcers (3 to 5 mm) were located between the nodules. Three patients had multiple large ulcers (1 to 2 em) along with nodules. The margins were irregular, swollen, and erythematous. At places the margins were studded with nodules. The base of the ulcer was covered with a whitish to yellowish exudate and showed a granular appearance. A stricture was seen in 10 patients (Fig. 3) where the colonic lumen appeared to be narrow. Nodules varying in size from 2 to 4 mm were seen at the strictured area. Multiple irregular-shaped small ulcers (0.5 to 1 em) were visible between the nodules. Three of these patients required surgery due to obstructive symptoms. In eight patients, a large number of mucosal nodules alone were present in a segment of colon 4 to 6 em in size. Pseudopolypoid edematous folds were encountered in two of eight patients. Histology
In 12 (41 %) patients biopsies established the diagnosis. The biopsy material revealed multiple confluent granulomas consisting of epitheloid and Langhans giant cells in six and the remaining six patients had caseation in addition to granulomas. At places the mucosa was infiltrated with chronic inflammatory cells. Biopsy specimens of the remaining patients revealed mild to moderate infiltration of the lamina propria with inflammatory cells composed of lymphocytes, plasma cells, and a few eosinophils. In some cases there was extensive ulceration of the mucosa and replacement by dense granulation tissue abundant in capillaries and plump fibroblasts. Biopsy specimens obtained at colonoscopy usually contained mucosa and muscularis mucosas and seldom the submucosa. Granulomas were identifical more frequently from an ulcerated lesion (48%) when compared with nodular lesions (25%). Bacteriology
Figure 1. Site of colonic involvement: two or more than two sites were involved in eight (28%) patients.
572
A total of 15 specimens was utilized for culture. Six (40%) of them yielded a positive culture on Lowenstein Jensen media. All the organisms were identified as Mycobacterium tuberculosis on the basis of colony characteristics and biochemical tests. Endoscopicbacteriologic correlation showed isolation of mycobacteria from three (50%) of six patients with nodular lesions, two (40%) of five patients with a stricture, and one (25%) of four patients with a nodular lesion combined with ulcerations. In the 15 patients who had simultaneous histologic and bacteriologic evaluation, four patients had both granulomas and positive cultures. In two patients mycobacteria were cultured in the absence of granulomas on biopsy. Three ofthe remaining nine patients GASTROINTESTINAL ENDOSCOPY
Table 1. Patient characteristics Patient Age/sex Chest x-ray
1 2 3 4 5 6 7 8 9 10 11
12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29
49/M 291M 30/F 241M 45/M 50/F 40/M 30/F 281M 291M 46/M 301M 341M 26/F 381M 311M 14/F 50/M 27/F 301M 34/F 321M 40/F 251M 331M 40/M 321M 45/F 31/F
Normal Abnormal Normal Abnormal Normal Abnormal Normal Normal Negative Normal Normal Normal Abnormal Normal Normal Normal Normal Normal Abnormal Abnormal Normal Abnormal Normal Abnormal Abnormal Normal Normal Normal Abnormal
Purified protein Colonoscopy derivative Positive Positive Positive Negative Positive Positive Positive Positive Negative Positive Positive Positive Positive Positive Positive Positive Negative Positive Positive Positive Positive Negative Positive Positive Positive Positive Positive Positive Positive
SNU· NU SNU NU N SNU NU SNU N SNU SNU NU SNU NU NU N NU NU N NU NU N SNU N NU N N SNU SNU
Histology Negative Negative Granuloma Granuloma Negative Negative Granuloma Granuloma Negative Negative Granuloma Negative Granuloma Negative Negative Granuloma Granuloma Negative Negative Negative Granuloma Granuloma Negative Negative Negative Granuloma Negative Negative Granuloma
Bacteriology
Negative Positive Negative Positive Negative Negative Negative Positive
Negative Negative Positive
Positive
Negative Positive Negative
Response to chemotherapy Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes b Yes Yes b Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes b Yes Yes Yes Yes Yes Yes
• S, stricture; N, nodules; U, ulcer. b Three patients with strictures who required operation; surgical specimens showed granulomas.
in whom cultures were negative also revealed granulomas. Thus, 9 (60%) of 15 patients had a diagnosis established by biopsy. Diagnostic accuracy
In 29 patients, histology and bacteriology confirmed the diagnosis in 41 % and 40%, respectively. Of the 15 patients in whom the colonoscopic appearance suggested the diagnosis, which was not proven by either histology or bacteriology, 4 had associated pulmonary lesions. The remaining 11 patients were diagnosed on the basis of absence of other diseases on biopsies with a response to anti-tuberculous treatment. Ten of these patients had a positive purified protein derivative skin test. Three of these 11 patients subsequently demonstrated tubercular lesions (granulomas) in surgical specimens (Table 1). DISCUSSION
Tuberculosis may involve any site in the gastrointestinal tract. However, it affects the ileum and ileocecal areas commonly. This may be due to the relative stasis and affinity of the tubercle bacillus for lymphoid tissue. The value of colonoscopy in the VOLUME 38, NO.5, 1992
diagnosis of ileocecal tuberculosis has been well established. 5- 9 Segmental colonic tuberculosis has been described in several case reports. 10- 14 In the present study, colonoscopic appearances included the presence of mucosal nodules and ulcers in a colonic segment of 4 to 8 em in length. Nodules of various sizes (2 to 6 mm) were either scattered or densely packed. Ulcers were either large (10 to 20 mm) or small (3 to 5 mm). They were located between the nodules. In addition, areas of stricture may be associated with mucosal nodules and ulcers. The presence of mucosal nodules with pseudopolypoid edematous folds also suggested tuberculous infection. Crohn's disease, colonic neoplasm, and amebiasis can simulate the findings of colonic tuberculosis. The characteristic changes in Crohn's disease include ulceration, cobblestoning, and strictures. I?, 18 Cobblestoning is seldom seen in colonic tuberculosis. Directed colonoscopic biopsies are helpful in differentiating colonic neoplasm from tuberculosis. Amebiasis can pose a difficulty in differentiation, particularly in developing countries. In contrast to tuberculosis, ulcers in amebiasis occur in areas of grossly normal mucosa. Biopsy specimens obtained from these lesions show the trophozoites of E. histolytica. 19,20 573
The yield of positive cultures was not related to the presence of granulomas as in 2 of the 15 patients; organisms were recovered from tissue showing inflammatory changes. This observation is important because routine culture of the biopsy tissue will increase the diagnostic yield. We did not study acid fast bacilli on histologic sections as they were rarely seen in our previous studies. 9 , 22 Ideally, the diagnosis of tuberculosis should be confirmed by histology and or isolation of mycobacteria. However, the endoscopic appearance alone may justify a trial of anti-tuberculous therapy in patients where the clinical suspicion of the infection is high.
REFERENCES
Figure 2. Colonoscopic view of mucosal nodules with ulcers. Figure 3. Colonoscopic photograph of a stricture with mucosal nodules and an ulcer.
Biopsies obtained from tuberculous lesions revealed granulomas in 12 of29 cases (41 %). Previous studies5, 9 and case reports 6 , 7, 10-14 have also demonstrated a similar incidence of granulomas. The diagnosis of tuberculosis requires the demonstration of caseating granulomas. However, in India, the presence of non-caseating granulomas may be diagnostic because caseation may be absent or may be present only in lymph nodes. 1, 9,21 Caseating necrosis may be absent in patients who have received anti-tuberculous therapy in the past. 1 Furthermore, the presence of granulomas may not be related to the morphologic patterns of mucosal nodules or ulceration since the ability to detect a granuloma on biopsy is made difficult by the submucosal location of the granuloma. 5 , 7, 8, 14 In the present study, Mycobacterium tuberculosis on culture was demonstrated in 40% of patients. The yield is similar to other studies reported by us in the past. 9,22 Saka?3 reported a higher positive rate (69%) by culture of an emulsion from endoscopic biopsies. 574
1. Tandon HD, Prakash A. Pathology of intestinal tuberculosis and its distinction from Crohn's disease. Gut 1972;13:260-9. 2. Tabrisky J, Lindstrom RR, Peters R, et al. Tuberculous enteritis, review of a protean disease. Am J GastroenteroI1975;63:4957. 3. Paustian FF, Marshall JB. Intestinal tuberculosis. In: Berk JE, ed. Bockus gastroenterology. Vol 3. Philadelphia: WB Saunders, 1985:2018. 4. Werbeloff L, Novis BH, Banks, et al. The radiology of tuberculosis of the gastrointestinal tract. Br J Radiol 1973;46:32936. 5. Aoki G, Nagasako K, Nakaey, et al. Fibercolonoscopic diagnosis of intestinal tuberculosis. Endoscopy 1975;7:113-21. 6. Bretholz A, Strasser H, Knoblauch M. Endoscopic diagnosis of ileocecal tuberculosis. Gastrointest Endosc 1978;24:250-1. 7. Franklin CO, Mohapatra M, Perillo RP. Colonic tuberculosis diagnosed by colonoscopic biopsy. Gastroenterology 1979;76:362-4. 8. Bhargava DK, Tandon HD. Ileocecal tuberculosis diagnosed by colonoscopy and biopsy. Aust NZ J Surg 1980;50:583-5. 9. Bhargava DK, Tandon HD, Chawla TC, et al. Diagnosis of ileocecal and colonic tuberculosis by colonoscopy. Gastrointest Endosc 1985;31:68-70. 10. Tishler JMA. Tuberculosis of the transverse colon. AJR 1979;133:229-32. 11. Panton ONM, Sharp R, English RA, Atkinson KG. Gastrointestinal tuberculosis. Dis Colon Rectum 1985;28:446-50. 12. Radhakrishnan S, Nakib BA, Shaikh H, Menon NK. The value of colonoscopy in schistosomal, tuberculous and amoebic colitis. Two years experience. Dis Colon Rectum 1986;29:891-5. 13. Zyngier FR, Liberal MHT, Dechoum A. Tuberculosis colitis manifested by Skip lesions of the colon (Letter). Gastrointest Endosc 1986;32:375. 14. Morgante PE, Gandara MA, Sterle E. The endoscopic diagnosis of colonic tuberculosis. Gastrointest Endosc 1989;35:115-8. 15. Shriniwas. Characterization of anonymous mycobacteria from clinical material. J All India Inst Med Sci 1975;1:11. 16. Vestal. Procedure for isolation and identification of mycobacteria. US Department of Health Education and Welfare, 1969. 17. Lockhart-Mummery HE, Morson BC. Crohn's disease of the large intestine. Gut 1964;5:493-509. 18. Geboes K, Vantrappen G. The value of colonoscopy in the diagnosis of Crohn's disease. Gastrointest Endosc 1975;22:1823. 19. Blumencranz H, Kasen L, Romeu J, et al. The role of endoscopy in suspected amoebiasis. Am J GastroenteroI1983;78:15-8. 20. Rozen P, Bartz M, Rattan J. Rectal bleeding due to amebic colitis diagnosed by multiple endoscopic biopsies: report of two cases. Dis Colon Rectum 1981;24:127-9. 21. Howell JS, Knapton PJ. Ileocecal tuberculosis. Gut 1964;5:5249. 22. Bhargava DK, Shriniwas, Chawla TC, et al. Intestinal tuberculosis: Bacteriological study of tissue obtained by colonoscopy and during surgery. J Trop Med Hyg 1985;88:249-52. 23. Sakai y. Colonoscopic diagnosis of intestinal tuberculosis. Mater Med Pol 1979;11:275-8.
GASTROINTESTINAL ENDOSCOPY
Endoscopic diagnosis of segmental colonic tuberculosis Dinesh K. Bhargava, MD, PhD, A. K. S. Kushwaha, PhD S. Dasarathy, MD, OM, Shriniwas, MD Prem Chopra, MD New Delhi, India
We report colonoscopic findings in 29 proven cases of segmental colonic tuberculosis. The colonoscopic appearances of tuberculosis included: mucosal nodules and ulcers, stricture with nodules and ulcerations, and mucosal nodules with or without pseudopolypoid folds. In 12 (41%) of 29 patients colonoscopy biopsies enabled a histologic diagnosis to be made on the basis of typical granulomas. Culture of biopsy tissue on Lowenstein Jensen media isolated Mycobacterium tuberculosis in six (40%) of 15 patients. Combined histologic and bacteriologic evaluation established the diagnosis in 60% of patients. We conclude that even though target biopsy is an effective method of diagnosis, antituberculous chemotherapy may be started on the basis of the endoscopic appearance if there is a high clinical suspicion of tuberculosis. (Gastrointest Endosc 1992;38:571-574)
Tuberculosis of the colon and rectum even though uncommon is not a rarity in India.! Its clinical manifestations are non-specific. 2,3 Segmental radiologic findings are often difficult to differentiate from other diseases. 3 ,4 Surgical biopsies have been required to establish the diagnosis. In the recent past, numerous reports have shown the value of colonoscopic biopsy for confirmation of intestinal tuberculosis. 5- 9 However, the value of colonoscopy has not been emphasized in segmental colonic tuberculosis, probably because this condition is less prevalent in developed countries. 1O-!4 The present study describes the endoscopic lesions and evaluates the value of directed biopsies in patients with proven colonic and rectal tuberculosis. MATERIALS AND METHODS
Between 1984 and 1991, 29 patients with colonic and rectal tuberculosis underwent colonoscopy. In each patient, the following data were recorded: history, clinical examination, hematologic investigation, tuberculin test, chest x-ray, barium meal or barium enema, colonoscopic findings, and Received July 16, 1991. For revision September 3, 1991. Accepted April 2, 1992. From the Departments of Gastroenterology, Microbiology, and Pathology, All India Institute of Medical Sciences, New Delhi, India. Reprint requests: D.K. Bhargava, MD, Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi 110029, India. VOLUME 38, NO.5, 1992
histologic and bacteriologic data on biopsy material. The colonoscopic diagnosis was either confirmed by histologic evidence of caseating or non-caseating granuloma or a positive culture for mycobacteria. Other criteria included the presence of an associated focus of tuberculosis elsewhere or an absence of other diseases on biopsies from the endoscopic lesions with a response to anti-tuberculous chemotherapy. Colonoscopy was carried out with Olympus model CF type LB2 or CFL 10. Eight to 10 biopsies were obtained in each patient. Histologic examination was conducted: sections of 4- to 5-/Lm thickness were sliced from paraffin blocks and stained with hematoxylin and eosin. Bacteriologic examination was performed: suitable (three to four biopsy pieces) tissue was collected aseptically in physiologic saline for isolation of organisms. The tissue obtained was cut up with scissors and ground by using a tissue grinder. Subsequently, it was subjected to concentration by the modified Hanks' method. I5 The tissue homogenate was utilized for smear examination and culture on Lowenstein Jensen media. The various biochemical tests performed for identification of the organisms have been described by Vestal. 16 RESULTS
There were 18 men and 11 women with a mean age of 34.2 years. The common symptoms were fever (86%), weight loss (86%), diarrhea (50%), constipation (41%), obstructive symptoms (21%), and rectal bleeding (70%). Hematological investigations revealed an elevated erythrocyte sedimentation rate in 90% patients (20 to 55 mm/hour). Tuberculin skin test using 571
one tuberculin unit of purified protein derivative (BCG Laboratories, Guindi Madras) was positive (> 10 mm in diameter) in 25 (86%) of 29 patients. Chest xray was abnormal in 10 (35%) of 29 patients. Four patients had pulmonary infiltration, four had thickened pleura, and two had calcified hilar lymph nodes. All of them had a barium enema which showed areas of narrowing or constricting lesions. Five of these patients had additional findings suggestive of ileocecal involvement (shortening and narrowing of the cecum, distortion of the ileocecal valve with stenosis in the pre-valvular segment of the ileum) on barium enema. Tuberculosis involved various anatomical segments of the colon as shown in Figure 1. Two or more segments were involved in eight (28%) patients. Four patients with primarily sigmoid colon tuberculosis had involvement of the ileocecal region in two and in one each, the ascending colon and splenic flexure were affected. Two patients with tuberculosis primarily involving the descending colon had additional lesions in the transverse colon and ileocecal region. Tuberculosis primarily of the splenic flexure in one patient simultaneously involved the ileocecal region. In one patient segmental tubercular lesions were present in the descending colon, transverse colon, and ileocecal region. The clinical findings in the 29 patients with colonic tuberculosis are as shown in Table 1. Colonoscopic findings
Eleven patients had mucosal nodules and ulcers in a colonic segment of 4 to 8 em. The nodules measured 2 to 6 mm and had a pink surface (Fig. 2). They were
scattered and at places densely packed. Friability of mucosa over the nodules was unremarkable. Multiple small ulcers (3 to 5 mm) were located between the nodules. Three patients had multiple large ulcers (1 to 2 em) along with nodules. The margins were irregular, swollen, and erythematous. At places the margins were studded with nodules. The base of the ulcer was covered with a whitish to yellowish exudate and showed a granular appearance. A stricture was seen in 10 patients (Fig. 3) where the colonic lumen appeared to be narrow. Nodules varying in size from 2 to 4 mm were seen at the strictured area. Multiple irregular-shaped small ulcers (0.5 to 1 em) were visible between the nodules. Three of these patients required surgery due to obstructive symptoms. In eight patients, a large number of mucosal nodules alone were present in a segment of colon 4 to 6 em in size. Pseudopolypoid edematous folds were encountered in two of eight patients. Histology
In 12 (41 %) patients biopsies established the diagnosis. The biopsy material revealed multiple confluent granulomas consisting of epitheloid and Langhans giant cells in six and the remaining six patients had caseation in addition to granulomas. At places the mucosa was infiltrated with chronic inflammatory cells. Biopsy specimens of the remaining patients revealed mild to moderate infiltration of the lamina propria with inflammatory cells composed of lymphocytes, plasma cells, and a few eosinophils. In some cases there was extensive ulceration of the mucosa and replacement by dense granulation tissue abundant in capillaries and plump fibroblasts. Biopsy specimens obtained at colonoscopy usually contained mucosa and muscularis mucosas and seldom the submucosa. Granulomas were identifical more frequently from an ulcerated lesion (48%) when compared with nodular lesions (25%). Bacteriology
Figure 1. Site of colonic involvement: two or more than two sites were involved in eight (28%) patients.
572
A total of 15 specimens was utilized for culture. Six (40%) of them yielded a positive culture on Lowenstein Jensen media. All the organisms were identified as Mycobacterium tuberculosis on the basis of colony characteristics and biochemical tests. Endoscopicbacteriologic correlation showed isolation of mycobacteria from three (50%) of six patients with nodular lesions, two (40%) of five patients with a stricture, and one (25%) of four patients with a nodular lesion combined with ulcerations. In the 15 patients who had simultaneous histologic and bacteriologic evaluation, four patients had both granulomas and positive cultures. In two patients mycobacteria were cultured in the absence of granulomas on biopsy. Three ofthe remaining nine patients GASTROINTESTINAL ENDOSCOPY
Table 1. Patient characteristics Patient Age/sex Chest x-ray
1 2 3 4 5 6 7 8 9 10 11
12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29
49/M 291M 30/F 241M 45/M 50/F 40/M 30/F 281M 291M 46/M 301M 341M 26/F 381M 311M 14/F 50/M 27/F 301M 34/F 321M 40/F 251M 331M 40/M 321M 45/F 31/F
Normal Abnormal Normal Abnormal Normal Abnormal Normal Normal Negative Normal Normal Normal Abnormal Normal Normal Normal Normal Normal Abnormal Abnormal Normal Abnormal Normal Abnormal Abnormal Normal Normal Normal Abnormal
Purified protein Colonoscopy derivative Positive Positive Positive Negative Positive Positive Positive Positive Negative Positive Positive Positive Positive Positive Positive Positive Negative Positive Positive Positive Positive Negative Positive Positive Positive Positive Positive Positive Positive
SNU· NU SNU NU N SNU NU SNU N SNU SNU NU SNU NU NU N NU NU N NU NU N SNU N NU N N SNU SNU
Histology Negative Negative Granuloma Granuloma Negative Negative Granuloma Granuloma Negative Negative Granuloma Negative Granuloma Negative Negative Granuloma Granuloma Negative Negative Negative Granuloma Granuloma Negative Negative Negative Granuloma Negative Negative Granuloma
Bacteriology
Negative Positive Negative Positive Negative Negative Negative Positive
Negative Negative Positive
Positive
Negative Positive Negative
Response to chemotherapy Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes b Yes Yes b Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes b Yes Yes Yes Yes Yes Yes
• S, stricture; N, nodules; U, ulcer. b Three patients with strictures who required operation; surgical specimens showed granulomas.
in whom cultures were negative also revealed granulomas. Thus, 9 (60%) of 15 patients had a diagnosis established by biopsy. Diagnostic accuracy
In 29 patients, histology and bacteriology confirmed the diagnosis in 41 % and 40%, respectively. Of the 15 patients in whom the colonoscopic appearance suggested the diagnosis, which was not proven by either histology or bacteriology, 4 had associated pulmonary lesions. The remaining 11 patients were diagnosed on the basis of absence of other diseases on biopsies with a response to anti-tuberculous treatment. Ten of these patients had a positive purified protein derivative skin test. Three of these 11 patients subsequently demonstrated tubercular lesions (granulomas) in surgical specimens (Table 1). DISCUSSION
Tuberculosis may involve any site in the gastrointestinal tract. However, it affects the ileum and ileocecal areas commonly. This may be due to the relative stasis and affinity of the tubercle bacillus for lymphoid tissue. The value of colonoscopy in the VOLUME 38, NO.5, 1992
diagnosis of ileocecal tuberculosis has been well established. 5- 9 Segmental colonic tuberculosis has been described in several case reports. 10- 14 In the present study, colonoscopic appearances included the presence of mucosal nodules and ulcers in a colonic segment of 4 to 8 em in length. Nodules of various sizes (2 to 6 mm) were either scattered or densely packed. Ulcers were either large (10 to 20 mm) or small (3 to 5 mm). They were located between the nodules. In addition, areas of stricture may be associated with mucosal nodules and ulcers. The presence of mucosal nodules with pseudopolypoid edematous folds also suggested tuberculous infection. Crohn's disease, colonic neoplasm, and amebiasis can simulate the findings of colonic tuberculosis. The characteristic changes in Crohn's disease include ulceration, cobblestoning, and strictures. I?, 18 Cobblestoning is seldom seen in colonic tuberculosis. Directed colonoscopic biopsies are helpful in differentiating colonic neoplasm from tuberculosis. Amebiasis can pose a difficulty in differentiation, particularly in developing countries. In contrast to tuberculosis, ulcers in amebiasis occur in areas of grossly normal mucosa. Biopsy specimens obtained from these lesions show the trophozoites of E. histolytica. 19,20 573
The yield of positive cultures was not related to the presence of granulomas as in 2 of the 15 patients; organisms were recovered from tissue showing inflammatory changes. This observation is important because routine culture of the biopsy tissue will increase the diagnostic yield. We did not study acid fast bacilli on histologic sections as they were rarely seen in our previous studies. 9 , 22 Ideally, the diagnosis of tuberculosis should be confirmed by histology and or isolation of mycobacteria. However, the endoscopic appearance alone may justify a trial of anti-tuberculous therapy in patients where the clinical suspicion of the infection is high.
REFERENCES
Figure 2. Colonoscopic view of mucosal nodules with ulcers. Figure 3. Colonoscopic photograph of a stricture with mucosal nodules and an ulcer.
Biopsies obtained from tuberculous lesions revealed granulomas in 12 of29 cases (41 %). Previous studies5, 9 and case reports 6 , 7, 10-14 have also demonstrated a similar incidence of granulomas. The diagnosis of tuberculosis requires the demonstration of caseating granulomas. However, in India, the presence of non-caseating granulomas may be diagnostic because caseation may be absent or may be present only in lymph nodes. 1, 9,21 Caseating necrosis may be absent in patients who have received anti-tuberculous therapy in the past. 1 Furthermore, the presence of granulomas may not be related to the morphologic patterns of mucosal nodules or ulceration since the ability to detect a granuloma on biopsy is made difficult by the submucosal location of the granuloma. 5 , 7, 8, 14 In the present study, Mycobacterium tuberculosis on culture was demonstrated in 40% of patients. The yield is similar to other studies reported by us in the past. 9,22 Saka?3 reported a higher positive rate (69%) by culture of an emulsion from endoscopic biopsies. 574
1. Tandon HD, Prakash A. Pathology of intestinal tuberculosis and its distinction from Crohn's disease. Gut 1972;13:260-9. 2. Tabrisky J, Lindstrom RR, Peters R, et al. Tuberculous enteritis, review of a protean disease. Am J GastroenteroI1975;63:4957. 3. Paustian FF, Marshall JB. Intestinal tuberculosis. In: Berk JE, ed. Bockus gastroenterology. Vol 3. Philadelphia: WB Saunders, 1985:2018. 4. Werbeloff L, Novis BH, Banks, et al. The radiology of tuberculosis of the gastrointestinal tract. Br J Radiol 1973;46:32936. 5. Aoki G, Nagasako K, Nakaey, et al. Fibercolonoscopic diagnosis of intestinal tuberculosis. Endoscopy 1975;7:113-21. 6. Bretholz A, Strasser H, Knoblauch M. Endoscopic diagnosis of ileocecal tuberculosis. Gastrointest Endosc 1978;24:250-1. 7. Franklin CO, Mohapatra M, Perillo RP. Colonic tuberculosis diagnosed by colonoscopic biopsy. Gastroenterology 1979;76:362-4. 8. Bhargava DK, Tandon HD. Ileocecal tuberculosis diagnosed by colonoscopy and biopsy. Aust NZ J Surg 1980;50:583-5. 9. Bhargava DK, Tandon HD, Chawla TC, et al. Diagnosis of ileocecal and colonic tuberculosis by colonoscopy. Gastrointest Endosc 1985;31:68-70. 10. Tishler JMA. Tuberculosis of the transverse colon. AJR 1979;133:229-32. 11. Panton ONM, Sharp R, English RA, Atkinson KG. Gastrointestinal tuberculosis. Dis Colon Rectum 1985;28:446-50. 12. Radhakrishnan S, Nakib BA, Shaikh H, Menon NK. The value of colonoscopy in schistosomal, tuberculous and amoebic colitis. Two years experience. Dis Colon Rectum 1986;29:891-5. 13. Zyngier FR, Liberal MHT, Dechoum A. Tuberculosis colitis manifested by Skip lesions of the colon (Letter). Gastrointest Endosc 1986;32:375. 14. Morgante PE, Gandara MA, Sterle E. The endoscopic diagnosis of colonic tuberculosis. Gastrointest Endosc 1989;35:115-8. 15. Shriniwas. Characterization of anonymous mycobacteria from clinical material. J All India Inst Med Sci 1975;1:11. 16. Vestal. Procedure for isolation and identification of mycobacteria. US Department of Health Education and Welfare, 1969. 17. Lockhart-Mummery HE, Morson BC. Crohn's disease of the large intestine. Gut 1964;5:493-509. 18. Geboes K, Vantrappen G. The value of colonoscopy in the diagnosis of Crohn's disease. Gastrointest Endosc 1975;22:1823. 19. Blumencranz H, Kasen L, Romeu J, et al. The role of endoscopy in suspected amoebiasis. Am J GastroenteroI1983;78:15-8. 20. Rozen P, Bartz M, Rattan J. Rectal bleeding due to amebic colitis diagnosed by multiple endoscopic biopsies: report of two cases. Dis Colon Rectum 1981;24:127-9. 21. Howell JS, Knapton PJ. Ileocecal tuberculosis. Gut 1964;5:5249. 22. Bhargava DK, Shriniwas, Chawla TC, et al. Intestinal tuberculosis: Bacteriological study of tissue obtained by colonoscopy and during surgery. J Trop Med Hyg 1985;88:249-52. 23. Sakai y. Colonoscopic diagnosis of intestinal tuberculosis. Mater Med Pol 1979;11:275-8.
GASTROINTESTINAL ENDOSCOPY